Dataset Information

ROS/JNK/C-Jun Pathway is Involved in Chaetocin Induced Colorectal Cancer Cells Apoptosis and Macrophage Phagocytosis Enhancement

ABSTRACT: There is an urgent need for novel agents for colorectal cancer (CRC) due to the increasing number of cases and drug-resistance related to current treatments. In this study, we aim to uncover the potential of chaetocin, a natural product, as a chemotherapeutic for CRC treatment. We showed that, regardless of 5-FU-resistance, chaetocin induced proliferation inhibition by causing G2/M phase arrest and caspase-dependent apoptosis in CRC cells. Mechanically, our results indicated that chaetocin could induce reactive oxygen species (ROS) accumulation and activate c-Jun N-terminal kinase (JNK)/c-Jun pathway in CRC cells. This was confirmed by which the JNK inhibitor SP600125 partially rescued CRC cells from chaetocin induced apoptosis and the ROS scavenger N-acetyl-L-cysteine (NAC) reversed both the chaetocin induced apoptosis and the JNK/c-Jun pathway activation. Additionally, this study indicated that chaetocin could down-regulate the expression of CD47 at both mRNA and protein levels, and enhance macrophages phagocytosis of CRC cells. Chaetocin also inhibited tumor growth in CRC xenograft models. In all, our study reveals that chaetocin induces CRC cell apoptosis, irrelevant to 5-FU sensitivity, by causing ROS accumulation and activating JNK/c-Jun, and enhances macrophages phagocytosis, which suggests chaetocin as a candidate for CRC chemotherapy.

SUBMITTER: Wang H

PROVIDER: S-EPMC8578663 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The c-Jun NH2-terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases that play critical roles in the pathological process in species ranging from insects to mammals. However, the function of JNKs in bacteria-induced intestinal inflammation is still poorly understood. In this study, a fish JNK (CiJNK) pathway was identified, and its potential roles in bacterial muramyl dipeptide (MDP)-induced intestinal inflammation were investigated in Ctenopharyngodon idella. The present CiJNK was found to possess a conserved dual phosphorylation motif (TPY) in a serine/threonine protein kinase (S_TKc) domain and to contain several potential immune-related transcription factor binding sites, including nuclear factor kappa B (NF-κB), activating protein 1 (AP-1), and signal transducer and activator of downstream transcription 3 (STAT3), in its 5' flanking regions. Quantitative real-time PCR results revealed that the mRNA levels of the JNK pathway genes in the intestine were significantly upregulated after challenge with a bacterial pathogen (Aeromonas hydrophila) and MDP in a time-dependent manner. Additionally, the JNK pathway was found to be involved in regulating the MDP-induced expression levels of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the intestine of grass carp. Moreover, the nutritional dipeptide carnosine and Ala-Gln could effectively alleviate MDP-induced intestinal inflammation by regulating the intestinal expression of JNK pathway genes and inflammatory cytokines in grass carp. Finally, fluorescence microscopy and dual-reporter assays indicated that CiJNK could associate with CiMKK4 and CiMKK7 involved in the regulation of the AP-1 signaling pathway. Overall, these results provide the first experimental demonstration that the JNK signaling pathway is involved in the intestinal immune response to MDP challenge in C. idella, which may provide new insight into the pathogenesis of inflammatory bowel disease.

Dataset Information

ROS/JNK/C-Jun Pathway is Involved in Chaetocin Induced Colorectal Cancer Cells Apoptosis and Macrophage Phagocytosis Enhancement

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure